| Objective:More recently,an important role of mast cells has been described in chronic inflammatory and autoimmune disorders which are often associated with fibrosis or sclerosis.The objective of this research is to explore the role of mast cells in renal fibrosis through unilateral ureteral obstruction which is used to simulate the clinical pathological process of renal fibrosis.In the research mast cells released its specific protease tryptase by triggering degranulation ways.Tryptase spread to the renal tubular epithelium through paracrine manner,and then activated protease activation-2 receptor(PAR-2) in the renal tubular epithelium.At the same time the accumulation of mast cells released a variety of adhesion molecules, cytokines and growth factors that promote fibrosis,such as the Epidermal Growth Factor(EGF).These factors and cells formed a complex network by their biological effects and then to promote fibroblasts proliferation and renal tubular epithelial mesenchymal transition,which breaked the dynamic balance of extra cellular matrix(ECM) and caused the ECM deposition.Eventually those could lead to the aggravating of renal fibrosis.Methods:The experiment choosed SD rats were equally distributed into three groups by random rule,namely UUO model group, control group,rapamycin treatment group.Next we selected six mice from every group on postoperative3,7,11,14 days and gathered the left kidney after caesarean.Eventually the kidney were produced into wax block to spare.Using the wood qrain eosin HE staining and Masson staining observed each group changes in pathology of rat kidney damage and the degree of collagen fibers.Detected mast cell markers of tryptase、PAR-2、EGF with the method of immuohisto chemistry(IHC),and discussed their infiltration level during renal interstitial fibrosis with model of unilateralureteral obstruction,and datas statistical analysed by SPSS17.0.Results:(1)HE staining:Observed each kidney tissue of HE staining, model group show n that inflammatory cells increased in the renal tubular interstitial, renal tubular cells were dilation and atrophy in different degree,renal interstitial ureteral obstruction with the extension of time widened, treatment group pathological changes to a lesser degree,the control group shown normal renal tubules and no interstitial inflammatory cell infiltration; rapamycin treatment group shown some tubular dilation and atrophy in interstitial inflammatory cell infiltration, but lesser pathological changes than model group.(2)Masson staining: the model group:renal interstitial fibrosis was sign ificant damage.we was seen a large number of blue collagen deposition, tubular was a significant dilation and atrophy.Each time point compared with significant differ ence(P<0.05);the control group,there were no significant fibrosis and pathological changes, among which almost no renal interstitial collagen deposition fiber dyeing, and each point in time was no difference(P>0.05);rapamycin treatment group shown that renal interstitial collagen fibers visible deposition of the blue, and the amount of collagen fibers extended with the extension of time, compared with model group significantly reduced(P<0.05), but it is still more than control group(P<0.05).(3)immunohistochemical method to detect renal interstitial tryptase, PAR-2,the change trend of EGF expression levels:(1)the model group: UUO mediated renal fibrosis in trypt ase, PAR-2, EGF with ureteral obstruction extension of time, the amount of protein expression gradually increased(P<0.05);(2)the control group: Tryptase were no strongly expressed in renal tissue each time point; PAR2 were merely weak or no expr essed in renal tubular epithelial cells; EGF was weakly expressed in renal interstitial, each point in time there was no significant difference(P>0.05);(3)rapamycin treatm ent group: after rapamycin treatment UUO mediated kidney fibrosis,tryptase, PAR-2and EGF protein expression reduced in the model group(P<0.05), but still higher compared with control group(P<0.05).Conclusion:During renal interstitial fibrosis with model of unilateral ureteral obstruction studied that the relevant role of mast cells and renal fibrosis mechanism.The results shown that the expression level tryptase,PAR-2, EGF of mast cell markers increased gradually in UUO model group,which proved that mast cells involved in the occurrence of renal interstitial fibrosis.Using statistical methods confirmed that tryptase,PAR-2,EGF of mast cell markers present positively associated,which shown that mast cell through tryptase-PAR-2-EGF this approach to participate in fibrosis.Rapamycin treatment group compared with model group expression decrease shown that rapamycin is to inhibit the action of the interstitial fibrosis. |
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